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      Hydrogels for Bioprinting: A Systematic Review of Hydrogels Synthesis, Bioprinting Parameters, and Bioprinted Structures Behavior

      systematic-review

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          Abstract

          Nowadays, bioprinting is rapidly evolving and hydrogels are a key component for its success. In this sense, synthesis of hydrogels, as well as bioprinting process, and cross-linking of bioinks represent different challenges for the scientific community. A set of unified criteria and a common framework are missing, so multidisciplinary research teams might not efficiently share the advances and limitations of bioprinting. Although multiple combinations of materials and proportions have been used for several applications, it is still unclear the relationship between good printability of hydrogels and better medical/clinical behavior of bioprinted structures. For this reason, a PRISMA methodology was conducted in this review. Thus, 1,774 papers were retrieved from PUBMED, WOS, and SCOPUS databases. After selection, 118 papers were analyzed to extract information about materials, hydrogel synthesis, bioprinting process, and tests performed on bioprinted structures. The aim of this systematic review is to analyze materials used and their influence on the bioprinting parameters that ultimately generate tridimensional structures. Furthermore, a comparison of mechanical and cellular behavior of those bioprinted structures is presented. Finally, some conclusions and recommendations are exposed to improve reproducibility and facilitate a fair comparison of results.

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          Most cited references119

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          Biofabrication: A Guide to Technology and Terminology

          Biofabrication holds the potential to generate constructs that more closely recapitulate the complexity and heterogeneity of tissues and organs than do currently available regenerative medicine therapies. Such constructs can be applied for tissue regeneration or as in vitro 3D models. Biofabrication is maturing and growing, and scientists with different backgrounds are joining this field, underscoring the need for unity regarding the use of terminology. We therefore believe that there is a compelling need to clarify the relationship between the different concepts, technologies, and descriptions of biofabrication that are often used interchangeably or inconsistently in the current literature. Our objective is to provide a guide to the terminology for different technologies in the field which may serve as a reference for the biofabrication community.
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            Research on the printability of hydrogels in 3D bioprinting

            As the biocompatible materials, hydrogels have been widely used in three- dimensional (3D) bioprinting/organ printing to load cell for tissue engineering. It is important to precisely control hydrogels deposition during printing the mimic organ structures. However, the printability of hydrogels about printing parameters is seldom addressed. In this paper, we systemically investigated the printability of hydrogels from printing lines (one dimensional, 1D structures) to printing lattices/films (two dimensional, 2D structures) and printing 3D structures with a special attention to the accurate printing. After a series of experiments, we discovered the relationships between the important factors such as air pressure, feedrate, or even printing distance and the printing quality of the expected structures. Dumbbell shape was observed in the lattice structures printing due to the hydrogel diffuses at the intersection. Collapses and fusion of adjacent layer would result in the error accumulation at Z direction which was an important fact that could cause printing failure. Finally, we successfully demonstrated a 3D printing hydrogel scaffold through harmonize with all the parameters. The cell viability after printing was compared with the casting and the results showed that our bioprinting method almost had no extra damage to the cells.
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              Engineering alginate as bioink for bioprinting.

              Recent advances in three-dimensional (3-D) printing offer an excellent opportunity to address critical challenges faced by current tissue engineering approaches. Alginate hydrogels have been used extensively as bioinks for 3-D bioprinting. However, most previous research has focused on native alginates with limited degradation. The application of oxidized alginates with controlled degradation in bioprinting has not been explored. Here, a collection of 30 different alginate hydrogels with varied oxidation percentages and concentrations was prepared to develop a bioink platform that can be applied to a multitude of tissue engineering applications. The authors systematically investigated the effects of two key material properties (i.e. viscosity and density) of alginate solutions on their printabilities to identify a suitable range of material properties of alginates to be applied to bioprinting. Further, four alginate solutions with varied biodegradability were printed with human adipose-derived stem cells (hADSCs) into lattice-structured, cell-laden hydrogels with high accuracy. Notably, these alginate-based bioinks were shown to be capable of modulating proliferation and spreading of hADSCs without affecting the structure integrity of the lattice structures (except the highly degradable one) after 8days in culture. This research lays a foundation for the development of alginate-based bioink for tissue-specific tissue engineering applications.
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                Author and article information

                Contributors
                Journal
                Front Bioeng Biotechnol
                Front Bioeng Biotechnol
                Front. Bioeng. Biotechnol.
                Frontiers in Bioengineering and Biotechnology
                Frontiers Media S.A.
                2296-4185
                06 August 2020
                2020
                : 8
                : 776
                Affiliations
                [1] 1Bioengineering and Health Technologies Unit, Minimally Invasive Surgery Centre Jesús Usón , Cáceres, Spain
                [2] 2Stem Cells Unit, Minimally Invasive Surgery Centre Jesús Usón , Cáceres, Spain
                [3] 3School of Industrial Engineering, University of Extremadura , Badajoz, Spain
                [4] 4Scientific Direction, Minimally Invasive Surgery Centre Jesús Usón , Cáceres, Spain
                Author notes

                Edited by: Jöns Gunnar Hilborn, Uppsala University, Sweden

                Reviewed by: Ngan F. Huang, Stanford University, United States; Marina Rubert, ETH Zürich, Switzerland

                *Correspondence: Enrique Mancha Sánchez emancha@ 123456ccmijesususon.com

                This article was submitted to Tissue Engineering and Regenerative Medicine, a section of the journal Frontiers in Bioengineering and Biotechnology

                Article
                10.3389/fbioe.2020.00776
                7424022
                32850697
                056cb1b4-7f18-45bb-9ae0-01ade94af7a5
                Copyright © 2020 Mancha Sánchez, Gómez-Blanco, López Nieto, Casado, Macías-García, Díaz Díez, Carrasco-Amador, Torrejón Martín, Sánchez-Margallo and Pagador.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 09 March 2020
                : 18 June 2020
                Page count
                Figures: 9, Tables: 5, Equations: 0, References: 142, Pages: 28, Words: 18651
                Categories
                Bioengineering and Biotechnology
                Systematic Review

                bioprinting,hydrogel,systematic review,biomaterial,bioink
                bioprinting, hydrogel, systematic review, biomaterial, bioink

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